may lab dual photoredox catalysis in organic chemistrymay.chem.uh.edu/links/2016-10-18...

MayLabDualPhotoredoxCatalysisinOrganicChemistry

Reviews:(a)Chem.Rev.2013,113,5322—5363(b)J.Org.Chem.2016,81,6898—6926(c)Acc.Chem.Res.2016,ASAP,DOI:10.1021/acs.accounts6b00351

Po-AnChen10/18/2016

RuII

N

N NN

NN

2+

Ru(bpy)32+

RuII

N

N NN

NN

N

N

N

N

N

N

2+

Ru(bpz)32+

IrIII

N

N N

Ir(ppy)3

IrIII

N

NN

N

Ir(ppy)2(dtbbpy)+

t-Bu

t-Bu

+

IrIII

N

NN

N

Ir[dF(CF3)ppy]2(dtbbpy)+

t-Bu

t-Bu

+F3C F

F

F

FF3C

MayLabDualPhotoredoxCatalysisinOrganicChemistryPo-AnChen10/18/2016

RuII

N

N NN

NN

2+

Ru(bpy)32+

•  AbsorpFonat452nm(visiblelight)•  Stable,long-livedexcitedstate(τ=1100ns)•  Singleelectrontransfer(SET)catalsyt•  EffecFveexcitedstateoxidantandreductant

•  MaxabsorpFonat375nm(visiblelight)•  Long-livedexcitedstate(τ=1.9μs)•  Singleelectrontransfer(SET)catalsyt•  EffecFveexcitedstateoxidantandreductant•  Tripletenergyof56kcal/mol-1

Advantages:Excitedspeciesservedasbothoxidantsandreductants.Lowcatalystloading.RadicalintermediatescouldbegeneratedatmildercondiFon.Organicmoleculesgenerallydonotabsorbvisiblelight.

IrIII

N

N N

Ir(ppy)3


MLCT=MetaltoLigandChargeTransfer.ISC=IntersystemCrossing

Ref:MacMillanetal.Chem.Rev.2013,113,5322—5363ForIr(ppy)3:MacMillanetal.J.Org.Chem.2016,81,6898—6926Jablonskidiagram:h^p://www.shsu.edu/~chm_tgc/chemilumdir/JABLON.GIF

RuII

N

N NN

NN

2+

RuIII

N

N NN

NN

3+

eg*

π*

t2g

Ru(bpy)32+

Ground State

MLCT+

ISC

eg*

π*

t2g

*Ru(bpy)33+

Excited Statelowest-energy triplet

MLCT state

oxidant

reductant

E1/2*II/I

= +0.77 V

E1/2III/*II

= −0.81 V

eg*

π*

t2g

Ru(bpy)3+

eg*

π*

t2g

Ru(bpy)3+

metalcenter

ligandcenter

452 nm

SimplifiedMolecularOrbitalDepicAonofRu(bpy)32+

Jablonskidiagram


Ru(bpy)32+ *Ru(bpy)3

2+

E1/2III/*II = −0.81 V

A

ARu(bpy)33+D

D

E1/2III/II = +1.29 V

D

D

E1/2*II/I = +0.77 V

Ru(bpy)3+

E1/2II/I = −1.33 V

A

AReductiveQuenchingCycle

OxidativeQuenchingCycle

OxidaAveandReducAveQuenchingCycleofRu(bpy)32+

Ru(bpy)32+

excitation λmax = 452 nm

*Ru(bpy)32+emissionquenching

λmax = 615 nmRu(bpy)32+Ru(bpy)33+

or Ru(bpy)3+

FluorescenceQuenching(Stern-Volmer)Studies

CommonoxidaFvequenchers:viologens,polyhalomethanes,dinitro-anddicyanobenzenesCommonreducFvequenchers:terFaryamines.

Ref:ModernMolecularPhotochemistry;Benjamin/Cummings:MenloPark,CA,1978


EarlyWork:

Ph

OSMe

Me

BF4

N

CO2Et

Me

EtO2C

MeMe

[Ru(bpy)3]Cl2Ph

O

Me99% yield

Kellogg, 1978 - Reductive desulfuration

Deronzier, 1984 - Photocatalytic Pschorr reaction

CO2HN2

CH3CN, hυ

[Ru(bpy)3]Cl2CH3CN, hυ

CO2H

OR

ONPhth

SePhR

R

O

R1

N-(acyloxy)phthalimide

HR

ClR

Hydro-decarboxylation

Chlorination

Phenyl-seleneylation

Conjugate addition

±e

99% yield

R

intermediate

Okada, 1991 - Reductive decarboxylation of redox-active esters

Ref:TetrahedronLeB.1978,19,1255—1258J.Chem.Soc.,PerkinTrans.21984,1093—1098J.Am.Chem.Soc.1991,113,9401—9402


Ref:JACS,2008,130,12886—12887Science,2008,322,77—80 JACS,2009,131,8756—8757

RecentlyWork:

Ph

O

Ph[Ru(byp)3]Cl2 (5 mol%)

LiBF4, i-Pr2NEt

275 W CFL bulb

50-98% yield, 4:1 to 10:1 dr13 examples

O

H H

O

Ph

O

Ph

(a) Yoon, 2008 - [2+2] Enone cycloadditions

H

O

R

CO2EtBrNH

NMeO

Me t-Bu

•TFA

(20 mol%)

photoredox catalyst (0.5 mol%),2,6-lutidine,visible light

H

O

RCO2Et

63-93% yield88-96% ee

12 examples

(b) MacMillan, 2008 - Asymmetric catalytic α-alkylation of aldehydes

CO2Et

CO2Et

(c) Stephenson, 2009 - Reductive dehalogenation of activated alkyl halides

NN

CO2Me

BrCO2Me

HBoc

[Ru(byp)3]Cl2 (2.5 mol%)HCO2H, i-Pr2NEt

14 W CFLN

NCO2Me

HCO2Me

HBoc

79-99% yield10 examples


Photoredoxcatalystswithoutco-catalysts

NetReducFveReacFon-ReducFonofElectron-DeficientOlefins-DehalogenaFon-ReducFonofHydrazidesandHydrazinesNetOxidaFveReacFon-OxidaFonofBenzylicAlcoholstoAldehydes-OxidaFveHydroxylaFonofArylboronicacids-NetNeutralReacFons-AtomTransferRadicalAddiFons(ATRA)Cycle.

Ref:MacMillanetal.Chem.Rev.2013,113,5322—5363J.Org.Chem.2016,81,6898—6926


Ref:MacMillanetal.JACS,2009,131,10875—10877JACS,2010,132,13600—13603ACIE,2015,54,9668—9672

PhotoredoxCatalysisandEnamineCatalysis:TheAsymmetricα-AlkylaAonofAldehyde

H

O

R

FGXphotoredox catalyst (0.5 mol%),

2,6-lutidine,visible light

H

O

RFG

organocatalyst (20 mol%)

NH

NMeO

Bn Me

•TFA

NH

NMeO

Me t-Bu

•TFA

examples of organocatalyst

H

O

R

Cyanoalkyation63-95% yield90-98% ee

±e OC

H

O

R

CF3

Trifluoromethylation61-86% yield93-99% ee

via:F

FF

H

O

RAr

Benzylation68-91% yield82-93% ee fac-Ir(ppy)3 H

O

RCN

R1

Ru(bpy)32+


GeneralMechanismofDualCatalysisSystem

Ref:MacMillanetal.Chem.Rev.2013,113,5322—5363ForIr(ppy)3:MacMillanetal.J.Org.Chem.2016,81,6898—6926

H

OR

R

N

NMeO

Me t-Bu

FG

R

N

NOMe

t-Bu Me

FG

Ru(bpy)32+

*Ru(bpy)32+

oxidantRu(bpy)3+

reductant

SET

OrganocatalyticCycle

PhotoredoxCatalyticCycle

FGX

FGX− +

SETvisiblelight

FG

Me t-Bu

MeON

N

RH

FGR

O

H

NH

NMeO

Me t-Bu

Si faceexposed


Ref:JACS,2009,131,10875—10877JACS,2010,132,13600—13603ACIE,2015,54,9668—9672

n-hex

O

H

94%, 92% ee

n-hex

O

Hn-hex

O

H

86%, 90% ee78%, 87% ee

BenzylationNO2

NO2NN

N Cl

CO2Etn-hex

O

H

CO2Et

93%, 90% ee

CO2Et

O

H

CO2EtCO2Et

n-hex

O

HPh

92%, 90% ee80%, 88% ee

CO2Et

Me

Trifluoromethylation

n-hex

CF2CF3

O

Hn-hex

O

H

F

C6F5

F

n-hex

CF2CO2EtO

H

73%, 96% ee 85%, 98% ee 89%, 99% ee

Cyanoalkyation

CN

O

H

Ph92%, 93% ee

CNn-hex

O

H

95%, 95% ee

n-hex

O

H

CNNMe

Ts

73%, 95% ee

Alkylation

Selectedexamplesofdualphotoredoxcatalystandorganocatalyst


Ref:Nature2016,532,218—222Science2007,316,582—585

O

R1Me

NR2

Arn

organocatalyst (20 mol%)[Ir[(dF(CF3)ppy]2(dtbbpy)]PF6 (1 mol%)

benzoic acid (0.4 eq), PhMe, white LED

O

n

R1 NR2

Ar52-92% yield64-90% ee

N

R1n

HN

radicaladdition

β-scission

N

n

HN

R1 NAr

R2

fast N

n

HN

R1 NAr

R2

NH2

N

N

Mes Mes

Nfast SET from carbazole "e− pool"

Rapid tautomerisationfrom enamine to imine

IrIII

N

NN

N

t-Bu

t-Bu

F3C F

F

F

FF3C

[Ir[(dF(CF3)ppy]2(dtbbpy)]+

organocatalyst

O organocatalyst (20 mol%)Ir(ppy)3 (1 mol%)

1,4-dicyanobenzeneDABCO, HOAc, H2O,

DMPU, 26 W CFL

O

CN82% yield50% ee

Asymmetric β-arylation of ketones

N

NH2N

NRR

3π-electronradical cation

H+

NRR

5π-electronβ-enaminyl radical

O

direct β-carbonylfunctionalization

via:

single-electronoxidation


Ref:JACS,2014,136,16986—16989ForIr(ppy)3:J.Org.Chem.2016,81,6898—6926

PhotoredoxCatalysisandthiolcatalyst:ACouplingofBenzylicEtherswithSchiffBases H H

OMe

C-H BDE = 85.8 kcal/mol

HS CO2Me

C-H BDE = 87.2 kcal/mol

Physcial properties that enable thiol-photo C-H activation

weak C-H bonds: activation via bond energies, H atom transfer

HS

O

OMe

base

*Ir(III)(ppy)2(dtbbpy)+

redox cat.photoinduced

e− proton-coupledelectron transfer

PCETS

O

OMe

thiyl radicalactivation mode

OMeCN

CN

photoredox catalystthiol catalyst

OMe

CN

NPh

OMe

photoredox catalystthiol catalyst

NPh

OMe

NHPh

OMe

β-amino ether(racemic)

Diret arylation of benzylic ethers with cyanoaromatics

Merger of benzylic ethers with Schiff bases via photoredox

NPh Ir(III)(ppy)2(dtbbpy)+Ir(II)(ppy)2(dtbbpy)

reductant

SET

NPh S CO2Me

HAT

HS CO2MeOMe MeO


Ref:Sanfordetal.JACS.2011,133,18566Chem.Rev.2010,110,1147

PhotoredoxCatalysisandPalladium:C-HArylaAonwithAryldiazoniumSalts

N

MePd(OAc)2 (5 mol%)

IPh PhBF4−

AcOH, 100 oC N

Me

Ph88%

w/ophotoredoxcatalystvia:

2 e−oxidant

"R+" PdIVN XL

PdIIN XL

R

X

N

Ru(bpy)3Cl2 (2.5 mol%)Pd(OAc)2 (10 mol%)

Ag2CO3 (0.1 eq)MeOH, 25 oC,

visible light

N

Ph76%

Me N2BF4

+

4 eq.

Me

via:

PdIIIN X

LPdII

N XL

Ph Ru(bpy)32+Ru(bpy)33+

SETPdIV

N XL

R

X

w/photoredoxcatalyst


Ref:Sanfordetal.JACS,2012,134,9034—9047Ru(bpy)32+

*Ru(bpy)32+

oxidantRu(bpy)3+

reductant

SET

CoppercatalyticCycle


SETvisiblelight

CuX(I)

F3C I

CF3 + I−

CuX2(II)

CF3

CuX2(III)F3C

B(OH)2 B(OH)2(X)

CuX2(III)F3CAr

CF3

R

B(OH)2CuOAc (20 mol%)

Ru(bpy)32+

CF3I, K2CO360 oC

R

CF3

PhotoredoxCatalysisandCopper:TrifluoromethylaAonofBoronicAcid

Mechanism:


PhotoredoxCatalysisandGold:CurrentStateoftheArtinthetransformaAon

Review:Gloriusetal,J.Org.Chem.2016,81,6898—6926

Cl(I)AuR3P

ArN2BF4(or Ar2IBF4)

photocatalystvisible light

Au(III)Cl

R3P Ar

Key Cationic Au(III)Arspecies

OHR

n

OR

nAr

PRH

O

RP

RAr

O

RRing Expansion P-H Bond

Functionalization

R Ar

R H

R TMSor

C(sp)-H BondFunctionalization

R1 R2H2O R1

O

Ar

R2

AlkyneHydration

B(OH)2

Ar

C(sp2)-C(sp2)Coupling

•

R2

CO2tBuR1

O

Ar R2

OR1

AllenoateCyclization

OH

RO

R

ArCyclization of

o-alkynylphenols

OH

R2

R3

R1R1

O

Ar

R3

R2

Meyer-SchusterRearrangement

n = 1-2

OR[Au]

Hvia:

•

R2

R1

O

O[Au]via:


Review:Gloriusetal,J.Org.Chem.2016,81,6898—6926

Au(I)L

Nu−Au

Nu

L

oxidation Au

Nu

LXX

Trans-metalationR-M/H

Au

Nu

LXR

ReductiveElimination

R

NuDifunctionalized

Prodcuts

Protodemetalation

H

Nu

Hydrofunctionalized Products

+Nu−

Nu

Nu

HomocoupledProducts

Au(I) L

NuAu(I)L

Nu H

HRadicalAddition

NuAu(II)LAr

NuAu(III)L

Ar

Ar

NuDifunctionalized

Products

π-system

ReductiveElimination

Au(I)/Au(III)CatalysisCycle

Ru(bpy)32+

*Ru(bpy)32+

oxidant

Ru(bpy)3+

reductant

SETPhotoredoxCatalyticCycle

SET

visiblelight

ArN2BF4-N2, -BF4− Ar

Ar

Mechanism


Ref:Chem.Rev.2013,113,5322—5363ForIr(ppy)3:J.Org.Chem.2016,81,6898—6926

PhotoredoxCatalysisandNickel:SelectedC-CbondformaAon

Br

Radical coupling partner

NickelCatalytic

Cycle

*Ir(III)oxidant

Ir(II)reductant

SET


visiblelight

LnNi0

Ni(II)Ln

BrAr

R R

Ni(III)LnAlkylBr

Ar

Ni(I)Ln Br

Ir(III)

SETR R

CO2H

R R

R

R

R

R

O

OH

RNPh

H

R

with Doyle

with Doyle

R

R

Si(cat)2−X+

R

R

BF3KMolander

Fensterbankand Goddard

Molander

±e Ni

ArX

R

R

Ar

R

CO2H

NHBoc

Br

R

[Ir[(dF(CF3)ppy]2(dtbbpy)]PF6 (2 mol%)NiCl2•glyme (2 mol%)

(S,S)-(4-tBu-C6H4)-semicorrin (2.2 mol%)

TBAI, Cs2CO3, 34 W blue LEDsR

Ar

NHBoc46-84% yield82-93% ee

Enan)oselec)vedecarboxyla)veC(sp2)-C(sp3)coupling


Ref:Science,2014,345,433—436JACS,2015,137,2195—2198Org.LeB.2015,17,3294—3297Chem.–Eur.J.2016,22,120—123

Molander’swork

BocN

Ar Ar Ar Ar73% 92% 0% 93%

R1

R2

BF3K+

BrIr cat. (2.5 mol%)

NiCl2•dme (5 mol%)dtbbpy (5 mol%)

1.5 eq Cs2CO3, 26 W CFL

R1

R2

ArR3

Ar:

OMe

CN NN

N

Cl

95% 80% 88%

JACS, 2015, 137, 2195—î2198

Chem. - Eur. J.2016,22,120— î123

CF3

Ar BF3K

BrR

CF3

ArR

CF3

Ar

Cl

CF3

Ar

NBoc

63% 56%

CF3

Ar

66%

*whenachiralligandwasemployedandcomputaFonalstudiessuggestthatrapiddissociaFonoccurs.

HRR

R

R

BF3 R

RNiLn

NiLn

single-electrontransmetalation

low EAct

High EAct

conventionaltransmetalation

Conventionalapproach

SETapproach

*high temp.*strong base*isomeriaztion*β-hydride elimination

*room temp.*lower barrier*regioselective*minimal side products


Ref:JACS,2016,138,475—478Alsosee:ACIE,2015,54,11414—11418Org.LeB.2016,18,1606—1609

Ru(bpy)32+. (2.5 mol%)NiCl2•dme (5 mol%)

dtbbpy (5 mol%)

hv, r.t.

R1

R2

SiO

O

2

HNR"R""2

BrR

R1

R2 R

Ar

Ar

Ar:

OMe 77% 94%

O

O Ar79%

Ru(bpy)32+. (2.5 mol%)NiCl2•dme (5 mol%)

dtbbpy (5 mol%)

hv, r.t.Si

O

O

2

H3N H2N (Het)Ar(Het)ArBr

N

N

R

CN

R

CF3 NH

OR

NH

R

NNBoc

RR

OH

89% 81% 75% 87%

53%85%

Molander’swork


Nature,2015,524,330—334JACS,2015,137,9531—9534Org.LeB.2016,18,876—879JACS,2016,138,1760—1763Science,2016,DOI:10.1126/science.aag0209

PhotoredoxCatalysisandNickel:SelectedC-XbondformaAon Br

R HOR1

[Ir[dF(CF3)ppy]2(dtbbpy)]PF6 (1 mol%)NiCl2(dtbbpy) (5 mol%)quinuclidine, K2CO3,

34 W blue LEDs

RO

R1


Dual photoredox Ni-catalyzed C-O crossing-coupling

BrR

[Ir[dF(CF3)ppy]2(dtbbpy)]PF6 (0.02 mol%)NiCl2(glyme) (5 mol%)

DABCO34 W blue LEDs

RN

R1


Dual photoredox Ni-catalyzed C-N crossing-coupling

HNR1

R2

R2

IR

[Ir[dF(CF3)ppy]2(dtbbpy)]PF6 (2 mol%)NiCl2(glyme) (10 mol%)

pyridine34 W blue LEDs

R

SR1


Dual photoredox Ni-catalyzed C-S crossing-coupling (Johannes and Oderinde)

HSR1

BrR

[Ru(bpy)3](PF6)2 (2 mol%)NiCl2(glyme) (5 mol%)

[(CH3)2CHCH2Si(cat)2][NH2(i-Pr)2]34 W blue LEDs

R

SR1


Dual photoredox Ni-catalyzed C-S crossing-coupling (Molander)

HSR1

RI [Ru(bpy)3](PF6)2 (1 mol%)

Ni(cod)2 (15 mol%)IPr (15 mol%), Et3N

34 W blue LEDs28-97% yield17 examples

Dual photoredox Ni-catalyzed synthesis of indolines (Jamison)

NHAc R1

RNAc

R1

Ni(III)LnROBr

Ar

Ni(II)LnROAr

intermediate

IrIII

N

NN

N

t-Bu

t-Bu

F3C F

F

F

FF3C

[Ir[(dF(CF3)ppy]2(dtbbpy)]+


Ref:Chem.Rev.2011,111,1846JACS,2014,136,13606—13609JACS,2015,137,11938—11941

O O

OTransition MetalCO2-Extrusion

Recombination

OTsuji-Saeguse CO2-Extrusion-Recombination: Enolate Allylation

NR

O

OPd(PPh3)4 (5 mol%)

[Ir(dF(CF3)ppy]2(dtbby)]PF6 (1 mol%)

blue LEDs NR


Tunge - Photoredox Pd-catalyzed decarboxylative allylation

XO

O R

NiCl2(glyme) (5 mol%)4,4'-dOMebpy (5 mol%)

[Ir(dF(CF3)ppy]2(dtbby)]PF6 (1 mol%)

blue LEDs XR


MacMillian - Photoreox Ni-catalyzed CO2 extrusion recombination

O Oanhydride (formed in situ)

PhotoredoxCatalysisandNickel:CO2Extrusion-RecombinaAon


Ref:JACS,2015,137,11938—11941

GeneralMechanismofCO2Extrusion-RecombinaAon

NO

O

OMe

Boc

Ni0Ln

Ni(II)O Ln

OMe

ONBoc

Ni(III) Ln

OMe

NBoc

CO2

Ni(I)Ln

NOBoc

Me

e−

Ir(III)

*Ir(III)Ir(II)

e−

visiblelight

-CO2recombination



SelectedexamplesofCO2Extrusion-RecombinaAon

NOBoc

PhN

OBoc

CNN

OBocN

OBoc

OMe

86% 83% 82% 72%

NC2H4Ph

OBocN

Ph

C2H4Ph

O

H

BocN

CyC2H4Ph

O

H

Boc76% 55% 58%

NOBoc

ONiL2

O

decarboxylation

NOBoc

O L2NiCO2

ringopening

NOBoc

O L2NiCO2

NOBoc

ONiL2

O

carbonylation

Ref:JACS,2015,137,11938—11941

ProposedMechanismBasedonCyclopropyl13C-labelingStudies


Ref:Yoonetal,JACS,2008,130,12886—12887JASC,2011,133,1162—1164

Ru(bpy)32+

*Ru(bpy)32+

oxidant

Ru(bpy)3+

reductantSET


SET

visiblelight

i-Pr2NEt

i-Pr2NEt

Ph

O O

R

Li

Ph

O O

R

Li

H H

O

Ph

O

R

Lii-Pr2NEt

H H

O

Ph

O

R

[2+2] cycloproduct

Ar

O

R[Ru(byp)3]Cl2 (2.5 mol%)

La(OTf)3, TMEDA

23 W CFLH

RO

Ar

(a) Yoon - Photoredox Lewis acid-catalyzed [3+2] cycloadditions

R

O

Ar

[Ru(byp)3](PF6)2 (5 mol%)Sm(OTf)3, i-Pr2NEt

blue LEDs


ORAr

ROH

Ar


(b) Xia - Photoredox Lewis acid-catalyzed reductive cyclization

(c) Yoon - Photoredox Lewis acid-catalyzed hetero-Diels Alder

Ph

OO

R

[Ru(byp)3]Cl2 (5 mol%)LiBF4, i-Pr2NEt

200 W W-filament bulb

O RH

Ph

O

H


(d) Yoon - Photoredox Lewis acid-catalyzed [2+2] cycloadditions

PhotoredoxCatalysisandLewisAcid:

TheradicalintermediatecouldbestabilizedbytheLewisacid=>suppressingback-electrontransfer


Ref:JACS,2015,137,11948—11941

H

O

CNBrNH

NMeO

Me t-Bu(20 mol%)

photoredox catalyst (0.5 mol%),2,6-lutidine,visible light

H

O

CN

OO O

O

1) NaBH4, (0 oC)

2) NaOH, reflux86%, 2 steps

OO

O

O

LDA, HMPA, -78 oC

OMe

OMeBr

OO

O

O

OMe

OMe

80% (4 steps)(—)-bursehernin>30:1 dr, 94% ee

ApplicaAons:

N

OO

OH

Boc

Cl

O

O±e Ni

N

OO

Boc

O

68% yield

1)

F

OMe

MgBr

2) 4M HCl in dioxane NH

O HOH

O

MeO

F

•HCl

(±)-edivoxetine•HCl

PhotoredoxNi-CatalyzedCO2extrusion-recombinaAon:


Ref:Acc.Chem.Res.DOI:10.1021/acs.accounts.6b00270

GeneralSet-upsforBatchandFlowPhotocatalyAcReacAons


Ideas

NNHTsbase, photocatalyst

O

X

2

R

NNHTs base, photocatalyst

Au

N2BF4

Rn

base, photocatalyst

Au

Thankyouforyoura^enFon

may lab dual photoredox catalysis in organic chemistrymay.chem.uh.edu/links/2016-10-18...

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